TY  - JOUR
A1  - Oehler, Beatrice
A1  - Brack, Alexander
A1  - Blum, Robert
A1  - Rittner, Heike L.
T1  - Pain Control by Targeting Oxidized Phospholipids: Functions, Mechanisms, Perspectives
JF  - Frontiers in Endocrinology
N2  - Within the lipidome oxidized phospholipids (OxPL) form a class of chemically highly reactive metabolites. OxPL are acutely produced in inflamed tissue and act as endogenous, proalgesic (pain-inducing) metabolites. They excite sensory, nociceptive neurons by activating transient receptor potential ion channels, specifically TRPA1 and TRPV1. Under inflammatory conditions, OxPL-mediated receptor potentials even potentiate the action potential firing rate of nociceptors. Targeting OxPL with D-4F, an apolipoprotein A-I mimetic peptide or antibodies like E06, specifically binding oxidized headgroups of phospholipids, can be used to control acute, inflammatory pain syndromes, at least in rodents. With a focus on proalgesic specificities of OxPL, this article discusses, how targeting defined substances of the epilipidome can contribute to mechanism-based therapies against primary and secondary chronic inflammatory or possibly also neuropathic pain.
KW  - oxidized phospholipids
KW  - TRP channel
KW  - ion channel
KW  - analgesia
KW  - pain therapy
KW  - nociception
KW  - therapeutic antibody
KW  - mimetic peptide
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223432
SN  - 1664-2392
VL  - 11
ER  - 
TY  - JOUR
A1  - Oehler, Beatrice
A1  - Kistner, Katrin
A1  - Martin, Corinna
A1  - Schiller, Jürgen
A1  - Mayer, Rafaela
A1  - Mohammadi, Milad
A1  - Sauer, Reine-Solange
A1  - Filipovic, Milos R.
A1  - Nieto, Francisco R.
A1  - Kloka, Jan
A1  - Pflücke, Diana
A1  - Hill, Kerstin
A1  - Schaefer, Michael
A1  - Malcangio, Marzia
A1  - Reeh, Peter W.
A1  - Brack, Alexander
A1  - Blum, Robert
A1  - Rittner, Heike L.
T1  - Inflammatory pain control by blocking oxidized phospholipid-mediated TRP channel activation
JF  - Scientific Reports
N2  - Phospholipids occurring in cell membranes and lipoproteins are converted into oxidized phospholipids (OxPL) by oxidative stress promoting atherosclerotic plaque formation. Here, OxPL were characterized as novel targets in acute and chronic inflammatory pain. Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) and its derivatives were identified in inflamed tissue by mass spectrometry and binding assays. They elicited calcium influx, hyperalgesia and induced pro-nociceptive peptide release. Genetic, pharmacological and mass spectrometric evidence in vivo as well as in vitro confirmed the role of transient receptor potential channels (TRPA1 and TRPV1) as OxPAPC targets. Treatment with the monoclonal antibody E06 or with apolipoprotein A-I mimetic peptide D-4F, capturing OxPAPC in atherosclerosis, prevented inflammatory hyperalgesia, and in vitro TRPA1 activation. Administration of D-4F or E06 to rats profoundly ameliorated mechanical hyperalgesia and inflammation in collagen-induced arthritis. These data reveal a clinically relevant role for OxPAPC in inflammation offering therapy for acute and chronic inflammatory pain treatment by scavenging OxPAPC.
KW  - chronic pain
KW  - ion channels in the nervous system
KW  - molecular medicine
KW  - pain
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158536
VL  - 7
IS  - 5447
ER  -